Tetrahydropalmatine is a tetrahydroprotoberberine isoquinoline alkaloid that is a primary active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis. The levo isomer of THP (L-THP) appears to contribute to many of the therapeutic effects of these preparations. The pharmacological profile of L-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, suggests that it may have utility for treating addiction. Clinical trials where L-THP was used for the treatment of cocaine and heroin addiction have promising results. The clinical trial is planned for the treatment of schizophrenia. L-Tetrahydropalmatine is recorded in the Chinese pharmacopoeia.

CC-115 is a recently identified inhibitor of the mammalian Target of Rapamycin Kinase (TORK) and DNA-Dependent Protein Kinase (DNA-PK). It is under investigation in phase II clinical trials for the treatment for Glioblastoma and in phase I trials for the treatment of prostate cancer, Ewing's, Osteosarcoma, Chronic Lymphocytic Leukemia and Squamous Cell Carcinoma of the Head and Neck.

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

Solcitinib (also known as GSK2586184 or GLPG0778) is a selective Janus kinase 1 (JAK1) inhibitor, for the treatment of psoriasis, lupus, and ulcerative colitis. Galapagos NV's collaboration with GlaxoSmithKline has hit a roadblock. It was reported that its Big Pharma partner had hit the brakes on a Phase II study of GSK2586184 for lupus after a first look at the data failed to demonstrate a positive effect. And an exploratory Phase I/II of the same drug for ulcerative colitis was put on hold as investigators review the program.

ADL5859 (or ADL-5859) is Adolor Corporation developed a novel, oral compound that targets the delta opioid receptor. Delta receptor agonists are thought to offer benefits over other approaches to the management of pain. ADL-5859 was in the phase II of clinical trial for the treatment of neuropathic pain, acute pain, and pain due to osteoarthritis of the knee and for patients with osteoarthritis. Further development of this drug as potential pain treatments was discontinued.

Novartis Oncology (previously Novartis) is developing WNT-974 (formerly LGK 974), a first-in-class selective small molecule inhibitor of O-acyltransferase. WNT-974 is under development for the treatment of cancers that are driven by the Wnt pathway in a Wnt ligand-dependent manner. Upon oral administration, WNT-974 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational acylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine, a membrane-bound O-acyltransferase (MBOAT), is required for the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion and activity. Wnt signaling is dysregulated in a variety of cancers

Ceralifimod (ONO-4641) is an oral, selective Sphingosine 1-phosphate receptor 1 and 5 agonist. It was studied in the phase 2 trials for the treatment of multiple sclerosis, however, further, development was discontinued.

LY3023414, an investigational drug, is a small molecule that that demonstrates activity against PI3K, mTOR, and DNA-PK in tumor cells, thereby inducing cell-cycle effects and inhibiting cancer cell viability. As shown in vitro LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway, one of the most frequently mutated pathways in cancer, leading to cancer progression and resistance to existing treatments. Downstream target inhibition by LY3023414 occurs rapidly via an intermittent “on/off” mechanism that may enhance the drug's clinical tolerability, which may in turn allow LY3023414 to overcome some of the toxicities associated with PI3K/mTOR inhibitors and potentially reduce the emergence of feedback mechanisms leading to resistance. The physicochemical and absorption properties of LY3023414 are favorable, as evidenced by the molecule's high solubility across a wide pH range and high oral bioavailability. On the basis of these findings, LY3023414 is currently being evaluated in clinical trials in patients with advanced cancer such as metastatic prostate cancer and non-small cell lung cancer in combination with other chemotherapeutic agents and in endometrial cancer as a monotherapy.

(R)-Mequitazine or V0162 (10-[(3R)-1-azabicyclo[2.2.2]oct-3-ylmethyl]-10H-phenothiazine) is an anticholinergic enantiomer of mequitazine, an existing oral racemic antihistamine commercialized for over 30 years. (R)-Mequitazine was found to be an antagonist at muscarinic acetylcholine receptors behaving as an inverse agonist. (R)-Mequitazine was investigated in clinical trials for the treatment of chronic obstructive pulmonary disease, asthma and urinary incontinence.

Amcasertib is an orally administered investigational agent designed to inhibit cancer stemness pathways, including Nanog, by targeting stemness kinases. Amcasertib is undergoing multiple Phase I and Phase II studies as monotherapy and combination therapy for treating a range of tumor types.